Bone remodelling and integration of two different types of short stem: a dual-energy X-ray - absorptiometry study.

PURPOSE: Different kinds of bone preserving hip stems have been created to assure a more physiological distribution of the strengths on the femur. The aim of this research is to evaluate the density reaction of the periprosthetic bone while changing the conformation of the prosthetic implant on dual-energy X-ray - absorptiometry (DXA). METHODS: This is a prospective, single-centre study assessing bone remodelling changes after implantation of two short hip stems, dividing the patients in two groups according to the implant used: 20 in group A, Metha (B-Braun), and 16 in group B, SMF (Smith and Nephew). All participants had a pre-operative and a post-operative (24 months) DXA evaluating the changes in bone mass density (BMD) occurred in the five Gruen's zones. RESULTS: Compared to the pre-operative value, differences in BMD percentage were statistically significant only in ROI 4 (p < 0.05), with an increase in both groups (9 and 18%, respectively). The average increase in BMD was of 7.3% and 7.2% in the 2 groups. CONCLUSION: According to our study, both stems have proved able to provide good load distribution across the metaphyseal region favouring proper system integration. Nonetheless, is certainly needed to perform other studies with longer follow-up and bigger populations to give strength to these conclusions.

Osmophobia in migraine classification: a multicentre study in juvenile patients.

AIMS: This study was planned to investigate the diagnostic utility of osmophobia as criterion for migraine without aura (MO) as proposed in the Appendix (A1.1) of the International Classification of Headache Disorders (ICHD-II, 2004). METHODS: We analysed 1020 patients presenting at 10 Italian juvenile headache centres, 622 affected by migraine (M) and 328 by tension-type headache (TTH); 70 were affected by headache not elsewhere classified (NEC) in ICHD-II. By using a semi-structured questionnaire, the prevalence of osmophobia was 26.9%, significantly higher in M than TTH patients (34.6% vs 14.3%). RESULTS: Osmophobia was correlated with: (i) family history of M and osmophobia; and (ii) other accompanying symptoms of M. By applying these 'new' criteria, we found an agreement with the current criteria for the diagnosis of migraine without aura (MO) in 96.2% of cases; 54.3% of previously unclassifiable patients received a 'new' diagnosis. CONCLUSIONS: In conclusion, this study demonstrates that this new approach, proposed in the Appendix (A1.1), appears easy to apply and should improve the diagnostic standard of ICHD-II in young patients too.

Contamination of revision procedures in patients with adverse tissues reaction to metal on metal implant.

OBJECTIVE: The aim of this study is to evaluate the incidence of infections in MoM total hip replacement revisions and to propose a therapeutic algorithm that can reduce the onset of this complication. Total hip arthroplasty is one of the most successful procedures performed annually in the world. As the population ages, the number of primary arthroplasty procedures performed each year is rising in conjunction with an increasing revision burden. Metal on Metal (MoM) total hip arthroplasties were reintroduced in over the last fifteen years to meet these needs, larger diameters, improved lubrication, better stability, increased ROM and wear properties of the bearing couple. These advantageous features have led to an exponential diffusion of MoM. Since over last decade, it has become evident that hip replacements with MoM bearing have significantly higher revision rates compared to those with Metal on Polyethylene. The common pathway for this failure mode appears to be increased wear or corrosion with excessive release of metal ions and nanoparticles. Complications such as elevated serum metal ion levels, aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL) and pseudotumours have all been well documented, but recent studies suggest increased risk of infection with MoM bearing surfaces. PATIENTS AND METHODS: We collect data from a cohort of 44 patients who underwent revision of total hip arthroplasty between 2014 and 2017 for the complication of MoM bearing. Studied by radiological images, blood tests, and intraoperative clinical status, part of the population was treated with one stage revision, while the other was treated with a two-stage revision. RESULTS: Results showed a difference in the occurrence of infections in the two populations. CONCLUSIONS: We consider it appropriate to perform two-stage revision in all case of failure of MoM replacement so as to allow to minimize the likelihood of infection in patients with damaged tissues by ALVAL, pseudotumour, and necrosis that could create an ideal environment for bacterial development.

Is there any difference between tapered titanium stems with similar geometry and hydroxyapatite coating?

PURPOSE: Several tapered stems with similar geometry and extensive hydroxyapatite coating have recently been introduced. It is not clear, however, whether they share the same design or whether they exhibit any difference that might affect their clinical performances. In this study, we analysed five tapered stems fully coated with hydroxyapatite to establish whether they exhibit similar geometric features and may therefore be used indifferently when a cementless stem is indicated. METHODS: The length of the stem, the coronal and sagittal diameters, the length of the stem shoulder and the metadiaphyseal angle were measured. The ratio between the proximal and distal coronal diameters of the stem and that between the proximal and distal cross-sectional areas were calculated as a flare index and tapered index, respectively. RESULTS: The proximal coronal diameter ranged between 24.9 and 28 mm in the smaller size and between 34 and 38.4 mm in the largest sizes. The proximal sagittal diameter ranged between 10.2 and 11.8 in the smallest size and between 14.4 and 17.2 in the largest. A significant difference was found between stems of different brands in the flare index, tapered index, length of stem shoulder and metadiaphyseal angle. CONCLUSIONS: Lookalike tapered stems with extensive HA coating actually exhibit significant differences in several geometric features potentially affecting their clinical performances. As a result, these stems should not be used indifferently, but rather they should be selected on the basis of the femoral morphology of the operated patient.

Low complication rates in Minimally Invasive Plate Osteosynthesis (MIPO) for proximal humeral fractures at 5 years of follow-up.

INTRODUCTION: Purpose of this study was to analyse the medium term follow-up of minimally invasive plate osteosynthesis (MIPO) for proximal humeral fractures in terms of postoperative shoulder function, radiological outcome and complications. METHODS: 76 consecutive patients with unstable proximal humeral fractures were treated using locking plate with a minimally invasive antero-lateral approach in two surgical centers. Constant score and radiographic evaluation of 74 patients were available at mean follow up of 5 years (minimum 4 years). RESULTS: Mean Constant score was 74 (range to 28-100). Results were comparable in the two centers. Younger patients registered significantly higher scores (p < 0.05). 20 patients (27%) developed complications. Subacromial impingement occurred in 16,2% of cases for varus malreduction (6,7%) and for too proximal plate positioning (9,5%). Primary screws perforation (2,7%), secondary perforation due to cut-out (1,4%), avascular necrosis (AVN) of humeral head (1,4%), partial resorption of greater tuberosity (2,7%), secondary displacement of the greater tuberosity (2,7%) and stiffness (2,7%) were observed. DISCUSSION AND CONCLUSIONS: Even at a medium term follow-up, MIPO for proximal humeral fractures ensured good and reproducible results for most common pattern of fractures. Major complications were lower respect to open procedures, because of soft tissue, deltoid muscle and circumflex vessels sparing.

Light-dependent interaction between Drosophila CRY and the clock protein PER mediated by the carboxy terminus of CRY.

BACKGROUND: The biological clock synchronizes the organism with the environment, responding to changes in light and temperature. Drosophila CRYPTOCHROME (CRY), a putative circadian photoreceptor, has previously been reported to interact with the clock protein TIMELESS (TIM) in a light-dependent manner. Although TIM dimerizes with PERIOD (PER), no association between CRY and PER has previously been revealed, and aspects of the light dependence of the TIM/CRY interaction are still unclear. RESULTS: Behavioral analysis of double mutants of per and cry suggested a genetic interaction between the two loci. To investigate whether this was reflected in a physical interaction, we employed a yeast-two-hybrid system that revealed a dimerization between PER and CRY. This was further supported by a coimmunoprecipitation assay in tissue culture cells. We also show that the light-dependent nuclear interactions of PER and TIM with CRY require the C terminus of CRY and may involve a trans-acting repressor. CONCLUSIONS: This study shows that, as in mammals, Drosophila CRY interacts with PER, and, as in plants, the C terminus of CRY is involved in mediating light responses. A model for the light dependence of CRY is discussed.

Modest decrements in plasma glucose concentration cause early impairment in cognitive function and later activation of glucose counterregulation in the absence of hypoglycemic symptoms in normal man.

To establish the glycemic threshold for onset of neuroglycopenia (impaired cognitive function, measured by the latency of the P300 wave), activation of hormonal counterregulation and hypoglycemic symptoms, 12 normal subjects were studied either under conditions of insulin-induced, glucose-controlled plasma glucose decrements, or during maintenance of euglycemia. A decrement in plasma glucose concentration from 88 +/- 3 to 80 +/- 1 mg/dl for 150 min did not result in changes in the latency of the P300 wave nor in an activation of counterregulatory hormonal response. In contrast, a greater decrement in plasma glucose concentration from 87 +/- 3 to 72 +/- 1 mg/dl for 120 min caused an increase in the latency of the P300 wave (from 301 +/- 12 to 348 +/- 20 ms, P less than 0.01), a subsequent increase in all counterregulatory hormones but no hypoglycemic symptoms. Finally, when plasma glucose concentration was decreased in a stepwise manner from 88 +/- 2 to 50 +/- 1 mg/dl within 75 min, the increase in the latency of the P300 wave was correlated with the corresponding plasma glucose concentration (r = -0.76, P less than 0.001). The glycemic threshold for hypoglycemic symptoms was 49 +/- 2 mg/dl. Thus, in normal man the glycemic threshold for neuroglycopenia (72 +/- 1 mg/dl) is greater than currently thought; the hormonal counterregulation follows the onset of neuroglycopenia; the hypoglycemic symptoms are a late indicator of advanced neuroglycopenia.

Diurnal preference, mood and the response to morning light in relation to polymorphisms in the human clock gene PER3.

PER3 gene polymorphisms have been associated with differences in human sleep-wake phenotypes, and sensitivity to light. The aims of this study were to assess: i) the frequency of allelic variants at two PER3 polymorphic sites (rs57875989 length polymorphism: PER3 4, PER3 5; rs228697 SNP: PER3 C, PER3 G) in relation to sleep-wake timing; ii) the effect of morning light on behavioural/circadian variables in PER3 4 /PER3 4 and PER3 5 /PER3 5 homozygotes. 786 Caucasian subjects living in Northern Italy donated buccal DNA and completed diurnal preference, sleep quality/timing and sleepiness/mood questionnaires. 19 PER3 4 /PER3 4 and 11 PER3 5 /PER3 5 homozygotes underwent morning light administration, whilst monitoring sleep-wake patterns and the urinary 6-sulphatoxymelatonin (aMT6s) rhythm. No significant relationship was observed between the length polymorphism and diurnal preference. By contrast, a significant association was observed between the PER3 G variant and morningness (OR = 2.10), and between the PER3 G-PER3 4 haplotype and morningness (OR = 2.19), for which a mechanistic hypothesis is suggested. No significant differences were observed in sleep timing/aMT6s rhythms between PER3 5 /PER3 5 and PER3 4 /PER3 4 subjects at baseline. After light administration, PER3 4 /PER3 4 subjects advanced their aMT6s acrophase (p < 0.05), and showed a trend of advanced sleep-wake timing. In conclusion, significant associations were observed between PER3 polymorphic variants/their combinations and both diurnal preference and the response to light.

Efficient and heritable functional knock-out of an adult phenotype in Drosophila using a GAL4-driven hairpin RNA incorporating a heterologous spacer.

We have developed a modified RNA interference (RNAi) method for generating gene knock-outs in Drosophila melanogaster. We used the sequence of the yellow (y) locus to construct an inverted repeat that will form a double-stranded hairpin structure (y-IR) that is under the control of the upstream activating sequence (UAS) of the yeast transcriptional activator GAL4. Hairpins are extremely difficult to manipulate in Escherichia coli, so our method makes use of a heterologous 330 bp spacer encoding sequences from green fluorescent protein to facilitate the cloning steps. When the UAS-y-IR hairpin is expressed under the control of different promoter-GAL4 fusions, a high frequency of y pigment phenocopies is obtained in adults. Consequently this method for producing gene knock-outs has several advantages over previous methods in that it is applicable to any gene within the fly genome, greatly facilitates cloning of the hairpin, can be used if required with GAL4 drivers to avoid lethality or to induce RNAi in a specific developmental stage and/or tissue, is useful for generating knock-outs of adult phenotypes as reported here and, finally, the system can be manipulated to investigate the trans-acting factors that are involved in the RNAi mechanism.

Relation between exertional ischemia and prognosis in mildly symptomatic patients with single or double vessel coronary artery disease and left ventricular dysfunction at rest.

The randomized multicenter trials indicate that survival in patients with coronary artery disease and left ventricular dysfunction is enhanced by surgical therapy compared with medical therapy. This beneficial effect of coronary bypass surgery was demonstrated in patients with either three vessel or left main coronary artery disease, but not in those with one or two vessel disease. To determine whether subgroups of mildly symptomatic patients with one or two vessel coronary artery disease and left ventricular dysfunction have an increased risk of death or cardiac events during medical therapy, 53 consecutive patients with angiographically defined one or two vessel disease and impaired left ventricular function (ejection fraction 20% to 40%) were studied by exercise electrocardiography (ECG) and rest and exercise radionuclide angiography. All but two patients had previous myocardial infarction, and all were asymptomatic or only mildly symptomatic during medical therapy. By univariate life table analysis, mortality during medical therapy was associated significantly with the ST segment response to exercise (p less than 0.05) and with both the exercise ejection fraction (p less than 0.05) and the magnitude of change in ejection fraction with exercise (p less than 0.005). In patients with an exercise ejection fraction greater than 30%, the probability of survival at 6 years was 97 +/- 3% (+/- SE) compared with a survival rate of 62 +/- 14% in the remaining subjects (p less than 0.005). Similarly, 6 year survival was 100% in patients whose ejection fraction increased from the value at rest but was only 74 +/- 10% in the remaining patients (p less than 0.005). Exercise capacity was not associated with survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Significance of abnormal blood pressure response during exercise-induced myocardial dysfunction after recent acute myocardial infarction.

The relation between exercise left ventricular ejection fraction and blood pressure (BP) responses after an acute myocardial infarction (AMI) was investigated. Twenty-eight to 37 days after an uncomplicated AMI, 224 consecutive patients underwent exercise radionuclide angiography in the 40 degrees semisupine position. In 180 patients (group A, 80%), BP increased more than 5 mm Hg every stage; in 44 patients, BP responses were abnormal; in 33 (group B, 15%), BP did not increase during 2 stages; in 11 (group C, 5%), it decreased more than 5 mm Hg after an initial increase. Ejection fraction did not differ significantly among the 3 groups at rest (51 +/- 13 in group A, 50 +/- 18 in group B, 47 +/- 13 in group C [difference not significant]) or at peak exercise (51 +/- 16% in group A, 46 +/- 19% in group B, and 43 +/- 16% in group C, [difference not significant]). Exercise-induced left ventricular failure or hemodynamic decompensation occurred in 22 patients. In these patients, ejection fraction at rest was 44 +/- 19% and decreased to 35 +/- 16% (p less than 0.05) with exercise. Only 9 of these patients (41%) had abnormal BP responses, with the other 13 (59%) showing a normal BP responses. The The 35 patients with abnormal BP responses in the absence of hemodynamic decompensation were asymptomatic, terminating exercise because of fatigue. The ejection fraction at rest and during exercise in these patients was similar to that in patients with normal BP responses.(ABSTRACT TRUNCATED AT 250 WORDS)

Frequency, characteristics and significance of supraventricular tachyarrhythmias detected by 24-hour electrocardiographic recording in the late hospital phase of acute myocardial infarction.

The incidence, characteristics and clinical significance of supraventricular tachyarrhythmias occurring in the late hospital phase of acute myocardial infarction (AMI) were assessed in 209 consecutive patients. Arrhythmias were quantified by 24-hour electrocardiographic recording 16 +/- 3 days after AMI, and were classified according to the degree of complexity in 5 classes. Class 0 = less than 5 premature beats/hr; class 1 = between 5 and 100/hr; class 2 = greater than 100/hr or repetitive premature beats; class 3 = atrial-junctional tachycardia; class 4 = atrial flutter-fibrillation. Supraventricular tachyarrhythmias classes 1 to 2 always occurred in the absence of symptoms in 86 patients (41%); supraventricular tachyarrhythmias classes 3 to 4 (paroxysmal, self-limiting, brief) occurred in 27 patients (13%), symptomatically in 6. The presence of supraventricular tachyarrhythmias classes 2 to 3 was related to age over 55 years and complex ventricular tachyarrhythmias (greater than 20 premature beats/hr, ventricular tachycardia) (both p less than 0.05). Increasing complexity of supraventricular tachyarrhythmias was significantly associated with presence and entity of cardiac enlargement and left ventricular dysfunction (both p less than 0.01). Patients with class 4 showed the most severe cardiac deterioration. During the 2 years after AMI, patients with classes 2, 3 and 4 had a higher incidence of acute pulmonary edema, New York Heart Association functional classes III to IV for congestive heart failure (both p less than 0.005) and a greater need of digitalis and diuretics (p = 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)

Study of the P300 and cerebral maps in subjects with multi-infarct dementia treated with cytidine.

A study of event-related P300 potential and cerebral EEG maps was performed in 20 patients affected by multi-infarct dementia (MID): 10 subjects were treated with placebo and 10 with cytidine. The trial was divided into three intervals. The patients, after a period of washout, were evaluated throughout the course of the trial by electrophysiological examination performed at baseline, after 90 min from the first IV injection, again after 30 days of IM therapy, and finally after 60 days of continued IM therapy. In the group treated with cytidine, the findings relevant to the study of the P300 showed a significant decrease in latency values compared to baseline (P less than 0.05 ANOVA) and an improvement. though not significant, in the amplitude values. Calculation of the mean relative power of EEG values showed a significant decrease in delta activity and an increase in alpha activity. In the subjects treated with placebo, no statistically significant variation was found in either P300 or EEG map recordings. On the basis of these investigations it has been demonstrated that the variations in the registrations can be correlated to the improved neuronal activity following treatment with cytidine.

Myocardial scintigraphy in acute myocardial infarction treated with systemic thrombolysis: how far are we from obtaining reliable information for rescue PTCA?

All noninvasive tests have an unsatisfactory accuracy in assessing patency of the infarct related vessel after systemic thrombolysis. In large infarctions, the prompt knowledge of the amount of jeopardized myocardium, as well as the eventual success of thrombolysis on the culprit lesion are major clinical needs in the subsequent decision making process, including the indication to rescue PTCA. Several reasons preclude a meaningful use of thallium scintigraphy in this setting: the most important one is the need to perform pre-thrombolytic images before the administration of the active agent, implying a delay in the administration of thrombolysis that is clinically not acceptable. SestaMIBI perfusion scintigraphy at rest seems more suitable in this regard. SestaMIBI practically does not redistribute in the myocardium, and this implies that after an administration at admission in the CCU, the pre-thrombolysis images can be acquired later, without any interference with the therapeutic schedule. The estimate of myocardial salvage can be obtained by the comparison of the perfusion pattern derived from a later sestaMIBI injection with the pre-lysis images. Both planar and tomographic reconstructions have satisfactory positive and negative predictive accuracy for the patency of the culprit vessel. Difficulties are related with the necessity of having this information timely; we describe a few protocols, appeared in the literature, that might contribute in solving such problems. SestaMIBI imaging in patients with acute myocardial infarction should be encouraged and extended, given its potential to represent one of the best tool to judge the amount of jeopardized myocardium, the obtained salvage, and to guide the decision making after systemic thrombolysis.

Better preservation of cognitive faculty in continuous ambulatory peritoneal dialysis.

We employed the so-called event-correlated potential (ECP) P300, a neurophysiological test which explores the circuits of attention and memory in the brain and is altered in subjects with a dismetabolic or degenerative encephalopathy, in order to evaluate the cognitive faculty in two groups of uremic patients [18 on continuous ambulatory peritoneal dialysis (CAPD), 15 on hemodialysis (HD)] comparable with respect to age and time on dialysis. The values of latency (msec) of P300 resulted in CAPD patients 356 +/- 26 in CZ (central zero electrodes) and 357.5 +/- 25 in PZ (parietal zero electrodes), not significantly different from the values in normal controls (341 +/- 14.5 in CZ and 340 +/- 15.6 in PZ) and in HD patients postdialysis (354 +/- 24.4 in CZ and 354 +/- 25.6 in PZ). On the contrary, the predialytic values of HD patients (384 +/- 25.6 CZ and 385 +/- 25.5 in PZ) were significantly different from the postdialytic values and from the values of CAPD patients and controls (p < 0.01). These results support the conclusion that HD is able to restore a normal cognitive faculty only transiently in the postdialytic phase, while CAPD maintains this important function steadily close to the normal range, thus being clearly better than HD.

Control of uremic neuropathy by equilibrium peritoneal dialysis.

Motor nerve conduction velocity (MNCV), sensory nerve conduction velocity (SNVC) and distal motor latencies times (DMLT) were evaluated both in upper and lower limbs in three groups of 15 patients of comparable age, treated respectively by extracorporeal dialysis (HD), continuous ambulatory peritoneal dialysis (CAPD) and combined peritoneal dialysis (CPD) for comparable sufficiently long periods. Moreover, MNCV was monitored longitudinally in two groups of patients shifted from CAPD to HD and vice versa. The results show a significant superiority of peritoneal dialysis and particularly of CAPD with respect to HD in controlling uremic neuropathy.

Age correlation in the bulbo-cavernosus reflex.

A study was conducted in 120 normal male subjects (age range 15-20 years) by testing the bulbo-cavernosus reflex (BCR). The mean latency +/- SD of the reflex was 32.9 +/- 0.7 ms. BCR latency values reported in subjects grouped according to age (15-20, 21-30, 31-40, 41-50, 51-60, 61-70) did not vary significantly for individuals between the ages of 15 and 50; whereas, the latency values for the older age groups (5th and 6th groups), were statistically significant. In conclusion, the authors attribute the increased latency associated with age to changes which occur in the fibres of the nerve pathways and emphasize the importance of collecting normative data according to age groups.

[From the great clinical studies to the management of the single patient. Medical therapy in the pre- and post-fibrinolytic era]. / Dai grandi studi clinici alla gestione del singolo paziente. La terapia medica nell'era pre e post-fibrinolitica.

Medical therapy of myocardial infarction has changed over the last 30 years. The "lag phenomenon", i.e. the time lapsing from the appraisal of a new, relevant scientific evidence and its practical adoption, has been variable, and different from one treatment to another. It has been very short for GP IIb/IIIa receptor inhibitors in candidates for urgent coronary angioplasty after myocardial infarction, short for ACE inhibitors, and it has been also short for the decrease in the prescription of calcium channel inhibitors after controversial scientific evidence. This time lapse has been long for beta-blockers, that only now are used quite extensively in Italy: from less than 10% of hospitalized patients during the early '80s, to over 60% nowadays. This evolution of medical therapy has been progressive and continuous, has not been divided into two eras, and thrombolysis seems to have little to do with it. The extensive introduction of thrombolysis has simply divided patients with acute myocardial infarction into two subgroups, very different for clinical characteristics: candidates for this therapy, and "others". Candidates for thrombolysis have a much better prognosis, but for a "paradox effect" they have been studied much more than the others. Now, the bulk of publications concerning patients undergoing thrombolysis carries the risk of spreading the concept that myocardial infarction has changed. We do not think that this corresponds to reality. Probably, the concepts that have guided medical therapy have been very similar and unchanged over the years, and both medical and surgical plus coronary angioplasty therapies are today much more appropriately used than yesterday.

Changes in auditory P3 event-related potentials in uremic patients undergoing haemodialysis.

A study on event-related P300 potential (ERPs) was performed in 20 patients suffering from chronic uraemia and undergoing haemodialysis in order to assessing the functioning of their cognitive processes. The patients were evaluated before and after a standard treatment of haemodialysis. The P300 potential was studied by means of the "oddball" paradigm and the acoustic modality. Moreover the patients' performance was assessed on the basis of the following psychological tests: the Mini Mental Test, the Number Connection Test and the Digit Span of the Wechsler Adult Intelligence Scale. A significant improvement in the P3 latency was demonstrated following the dialysis treatment. Even though a slight improvement in the N2-P3 deflexion amplitude was recorded after dialysis, it was not statistically significant. These data indicate a positive modification in the speed of the cortical function as a consequence of dialysis. These results suggest that the P3 latency obtained from auditory stimuli can help to assess the benefits obtained through extracorporeal dialysis, especially in the follow-up to the illness.

[Guidelines: some considerations on one of the cultural instruments on which the switch in the National Health System can be based]. / Le linee guida: alcune considerazioni su uno degli strumenti culturali su cui si potrebbe fondare la svolta del Sistema Sanitario Nazionale.

In the last few years there has been an explosion of interest in guidelines, reflected in a vivid debate in the international literature. Guidelines for medical practice are not innovative tools, since their history began at least 20 years ago. They are produced with increasing frequency in North America, and similar developments are taking place in Europe. The concept of improving the quality of the services in the National Health System through the production and implementation of valid clinical guidelines has been recognized in Italy by the Ministry of Health, who introduced such a concept in the last reform of the law on the Sanitary Health System. Many international authors deem that clinical guidelines are a way to support effective clinical practice. If this still holds, and we believe it does, then we must ensure that these guidelines are effective. Also for the enthusiast, the entire process from the development to the dissemination, implementation, and evaluation is not an easy task. Guidelines should be written correctly by a multidisciplinary panel of experts, should be peer reviewed and updated. Guidelines should become the common field in which the four major parties of the sanitary "market" (a market far from ideal today) meet: the patient, the doctor, the manager, and the industry involved in medical technology. Guidelines should be disseminated and implemented: simply having evidence available does not necessarily mean that it will be used. Thus, the key question is not so much related to the acceptance of best practice, but the extent to which a guideline is cost-effective. In this review we have tried to discuss such points, taking into consideration all the steps, the discussions, the controversial points, and the unsolved questions which are smoldering under both the potential benefit of practice guidelines (also in the light of appropriateness of medical practice), and all the possible effects on clinical autonomy, health care costs, clinical practice satisfaction, legal implications, and conflicts of interest. It is crucial for medical associations, and indeed for all physicians, to take up this problem and constructively try to play an active part in the process, avoiding the possibility that controversial guidelines be imposed by the regulatory authorities.